Recklinghausen's disease: causes, symptoms and treatment

Recklinghausen's disease, or type I neurofibromatosis, is a disease with genetic origins characterized by development multiple tumors, skin lesions in the form of "coffee with milk" spots, freckled rashes in atypical areas and a number other symptoms. The disease is quite widespread among the world's population. Has a progressive nature and is incurable. Only symptomatic treatment is performed. Specific treatment is currently under development. From this article you can learn about the causes, symptoms, diagnostics and methods of treatment of Recklinghausen's disease.

The disease has a lot of synonyms: peripheral neurofibromatosis, neurofibrolypomatosis, classical neurofibromatosis, gliophybromatosis, ontogenic dystrophy, congenital neuroectodermal dysplasia of Van-Bogart, disease Watson. The historical name "Recklinghausen's disease" is rooted in 1882, when the symptoms of neurofibromatosis were first described by Friedrich von Recklinghausen.

Prevalence of the disease

Recklinghausen's disease is considered a very common disease. Frequency of occurrence is 1 case for 2500 - 7800 population. This is a very high figure. This is the most common disease with a genetic nature. Moreover, in connection with the transfer of inheritance, there is no trend towards a decrease in prevalence rates.

Diseases are susceptible to both men and women. Race does not matter. There is no dependence on a geographical place of residing, features of a feed and other factors.

Reklinghausen's Disease

In the 90 years of the last century, the exact genetic cause of the disease was established: mutations in one of the genes of the 17th chromosome.

The gene is responsible for the production of proteins that suppress tumor growth in the human body. That is, normally, when a tumor cell arises in the body, it is recognized by the immune system and destroyed. With Recklinghausen's disease, such a tumor cell remains to live and develop, multiplying and becoming a large tumor. Usually there are benign neoplasms. However, in 3-15% malignancy and the formation of cancer cells are possible. In general, the risk of malignant tumors in patients with type I neurofibromatosis is higher than in the population 200-500 times.

The gene has huge dimensions in comparison with others. This feature causes a high frequency of new mutations. About 50% of all cases of Recklinghausen's disease are hereditary (that is, a mutation occurred in one from generations earlier and simply transmitted to descendants), the second half is the result of new spontaneous mutations.

A peculiarity of Recklinghausen's disease is that the resulting mutation has a high degree of clinical manifestation (penetrance), that is, it makes itself felt in almost 100% of cases. It can not remain unnoticed throughout the life of the person, the carrier of this mutation.

The disease is transmitted by inheritance according to the autosomal dominant type, including newly emerging mutations. This type of transmission means no connection with the sex and the realization of the effect even in the presence of only one defective gene (all human genes are paired). The second normal gene in this case is not able to "defeat" the defective one.

Recklinghausen's Disease Symptoms

Recklinghausen's disease is characterized by the breadth and variety of clinical manifestations. Among them, it is customary to distinguish tumor growths, skin disorders, pathology of the musculoskeletal system and the nervous system.

Skin disorders

A specific feature of type I neurofibromatosis is pigmented spots on the skin of the color "coffee with milk." They can be detected already at birth, and may appear in childhood. Are flat, painless areas of the skin from light beige to dark brown and even gray-blue in different locations and sizes. Most often they are located on the skin of the trunk and extremities. To the touch, the skin in such areas does not differ from normal. Spots are permanent, do not tend to discoloration or disappearance. But in fact almost every person has a birthmark or even a few, which does not mean the presence of neurofibromatosis. For Recklinghausen's disease, the number of such spots plays a role: in an adult, they must be at least 6 mm in size, 15 mm or more. Only in this case it serves as a diagnostic criterion for this disease.

Another skin manifestation are freckled rashes in the form of "bunches". They are located in atypical places: in the armpits, inguinal areas, popliteal pits. They, as well as the spots of the color of "coffee with milk appear throughout life. Usually, their occurrence is associated with a provoking factor: friction clothing, microtrauma, intertrigo. Freckles on the face are not considered a manifestation of the disease.

Another typical for Recklinghausen's disease is the pigmentation of Lisch's nodules (gamarthroma). This pigmentation spots are whitish in the iris of the eye. They are not visible to the naked eye, but are revealed when viewed in a slit lamp. In themselves, Lisa's nodules do not cause anxiety. After 20 years of age, they are found in more than 95% of patients, and therefore are considered a specific feature of Type I neurofibromatosis. It is the nodules of Lisha that become a reliable evidence of Recklinghausen's disease when performing differential diagnosis with other types of neurofibromatosis.

Tumor growths

Neurofibromas can be located in any part of the body and have different sizes.

With illness Recklinghausen formed a large number of tumor growths - the neurofiber. They are multiplying cells of peripheral nerve membranes. Neurofibromas look like nodules (nodes - depending on the size), they can grow on a pedicle or on a wide base. Nodules may not differ in color from the rest of the skin, but may have a reddish-violet color. At the top of some of them can grow hair.

The amount of neurofibromus depends on the age of the patient: in childhood they are very few, with the onset of the period of puberty they grow, like mushrooms after the rain. The number of neurofibromes in each patient is different. They can, in the literal sense of the word, cover the entire body, and can be single. After 30 years, neurofibromas are found in 94% of patients.

Dimensions of the neurofibre are also variable: from a few millimeters to a meter in diameter. In this regard, they can disfigure limbs and individual parts of the body, causing ugliness. Neurofibromas can cause abnormal enlargement of the limbs, which is called elephantiasis. When placed inside the body, they squeeze the internal organs, disrupting their function, so the symptoms manifestations of such neurofibres are very diverse, since tumors can be located in any part organism. This cough and shortness of breath with the growth of neurofibroma in the area of ​​the tracheobronchial tree, this is a violation of digestion when localized in the area of ​​the gastrointestinal tract and so on.

Among the neurofibromas the following varieties are distinguished;

• dermal: not soldered with the underlying tissues, are displaced relative to the underlying tissues;
• subcutaneous: more dense and immobile formations;
• plexiform: develop on large nerves, often reach a gigantic size.

When involved in the tumor process of the nerve roots, neurofibromas are accompanied by a neurological symptomatology: pain, impaired sensation, muscle weakness in the corresponding nerve sites.

Neurofibromas are benign neoplasms, but in 3-15% of cases they can be transformed into malignant ones.

In addition to neurofibroma, in patients with Recklinghausen's disease, the frequency of occurrence is higher than in the population other tumors (especially the nervous system): astrocytomas, meningiomas, ependymomas, gliomas of the visual nerve. Developing inside the skull, they cause increased intracranial pressure, muscle weakness (paresis), loss of sensitivity, speech, vision, hearing, and mental disorders. Quite often a finding in the illness of Recklinghausen is pheochromocytoma, a tumor of the adrenal glands that causes an uncontrolled increase in blood pressure.

Glioma of the optic nerve is found in 15% of patients. The tumor initially does not give any manifestations, and as it grows, it can cause a decrease in vision, pain and protrusion of the eyeball, the omission of the eyelid. A feature of gliomas of the optic nerve is the tendency to recur, even after complete, seemingly surgical removal.

Changes from the nervous system

Neurological disorders in Recklinghausen's disease (except for symptoms caused by compression of the brain neurofibromas and other tumors in the nervous system) are represented by mental disorders of varying degrees expression. A slight decrease in intellectual abilities, difficulties in mastering the exact sciences, acquisition writing and reading skills is a list of the most common problems in neurofibromatosis I type.

Quite often in Recklinghausen's illness are epileptic seizures, depression and accompanying symptoms. Sometimes psychological disorders are associated with cosmetic defects that arise because of the large amount of neurofibroma. Patients shy of their appearance, become isolated in themselves, which is the cause of mental disorders and behavior.

Disturbances of the musculoskeletal system

The disease is characterized by the presence of an irregular structure of some bones of the body. Among the most common anomalies of the osseous system it is worth noting the following:

• underdevelopment of the wing of the sphenoid bone;
• kyphoscoliotic deformation of the spine;
• defects along the edges of the vertebral bodies, the lower edges of the ribs;
• non-growth of vertebral arches;
• widening of intervertebral foramen;
• spondylolisthesis (displacement above the underlying vertebra with respect to the underlying one);
• deformation of the chest;
• skull asymmetry, large skull (macrocephaly);
• craniovertebral anomalies (eg, basilar impression);
• pseudoarthrosis (as a result of frequent fractures);
• cysts of tubular bones;
• deformation of tubular bones (for example, shin bones).

In some cases, the anomalies of the spine are combined with meningocele - hernial protrusion of the membranes of the brain.

Other symptoms

There are a number of changes on the part of the body that are registered with Recklinghausen's disease. They occur less frequently than the described symptoms, however, they are diagnostically valuable signs. These are the following changes:

• growth impairment;
• endocrine disruption of puberty (premature puberty, gynecomastia);
• narrowing of the renal and / or pulmonary arteries;
• pulmonary cysts;
• syringomyelia.

Diagnostics

There are diagnostic criteria for the International Committee of Experts on Neurofibromatosis. For a reliable diagnosis of "Recklinghausen's disease the patient should have at least 2 symptoms from the following:

• 5 or more "coffee and milk" spots more than 5 mm in diameter to adolescence and 6 or more such spots more than 15 mm in diameter after puberty;
• two any neurofibromas (or one plexiform);
• presence of freckles in axillary and inguinal folds;
• underdevelopment of the wing of the sphenoid bone or thinning of the cortical layer of tubular bones with the formation of pseudoarthrosis or without it;
• glioma of the optic nerve;
• at least two nests of Lisha;
• similar changes in one of the relatives of the first line of kinship (parents, children, sisters and brothers).

To establish an accurate diagnosis, a consultation of narrow specialists is necessary: ​​the oculist, the dermatologist, the neurologist, the surgeon (if necessary - the oncologist), genetics, the traumatologist-orthopedist, the neurosurgeon. The list of additional research methods used to diagnose Recklinghausen's disease is quite wide. The choice of method depends on the localization of pathological changes.

If a patient is diagnosed with such a diagnosis, relatives should be carefully examined, in view of characteristics of hereditary transmission of the disease (about 50% of relatives are likely to be also patients). It should be borne in mind that the process of the appearance of various symptoms in Recklinghausen's disease is quite dynamic. This means that the absence of many symptoms at present does not guarantee their absence in the future. Therefore, periodic examinations are recommended to exclude this pathology.

Treatment

Recklinghausen's disease is still an incurable disease. All methods of care are classified as symptomatic, which help to eliminate a number of signs and pathological changes.

The main method of treatment is surgical removal of the neurofibre. It is carried out in cases of large tumors that squeeze individual structures and lead to their violation functions (for example, an obstacle to normal movement in the presence of a tumor on the lower limb that caused elephantiasis). In a number of cases, the compression of the nerves by the nodes of the neurofibre leads to a pronounced pain syndrome, the formation of paresis and sensitivity disorders. This situation is also an indication for surgical intervention. Also, surgical treatment is used for cosmetic purposes, when neurofibromas cause disfigurement. Surgical treatment is possible only in cases of a small number of tumors. Multiple neurofibromas located on a small area can not be radically removed.

In cases where a patient is diagnosed with a malignant tumor, the treatment is performed using all existing methods in oncology. Chemotherapy, radiation therapy in combination with surgical removal of the tumor. Features of treatment will depend on the type of tumor.

At the stage of clinical study, there are currently such drugs as Tipipharnib and Pirfenidone. But until the tests are completed completely, the drugs can not be recommended for the treatment of Recklinghausen's disease.

Forecast for Recklinghausen's disease

Type I neurofibromatosis is a disease with an unclear prognosis, because there are no clear criteria to reliably predict the course of the disease. What size will the tumors be, where they will be located, how they will behave during life, whether there will be a relapse of the removed tumor - these questions can not be answered. It is known only that pregnancy provokes an increase in the number of neurofibromas.

Benign tumors do not carry a risk to life, but if the process turns into malignant, then the prognosis worsens.

The life expectancy of patients with type I neurofibromatosis, on average, corresponds to that in the population (with the exception of cases of tumor degeneration into malignant tumors).

Thus, Recklinghausen's disease is a common genetic problem of mankind. This disease with a multifaceted clinical picture, in which the most common is the damage to the skin, the nervous system with the development of a variety of tumors. The disease is inherited. The main method of treatment is now the surgical method, but several drugs are being studied that can help such patients more effectively.

Educational program on neurology, lecture on the topic "Neurofibromatosis